title: RTOG 0518: randomized phase III trial to evaluate zoledronic acid for prevention of osteoporosis and associated fractures in prostate cancer patients.
abstract: BACKGROUND
  RTOG 0518 evaluated the potential benefit of zoledronic acid therapy in preventing bone fractures for patients with high grade and/or locally advanced, non-metastatic prostate adenocarcinoma receiving luteinizing hormone-releasing hormone (LHRH) agonist and radiotherapy (RT).
  
  
  METHODS
  Eligible patients with T-scores of the hip (<-1.0, but >-2.5 vs >-1.0) and negative bone scans were prospectively randomized to either zoledronic acid, 4 mg, concurrently with the start of RT and then every six months for a total of 6 infusions (Arm 1) or observation (Arm 2). Vitamin D and calcium supplements were given to all patients. Secondary objectives included quality of life (QOL) and bone mineral density (BMD) changes over a period of three years.
  
  
  RESULTS
  Of 109 patients accrued before early closure, 96 were eligible. Median follow-up was 36.3 months for Arm 1 and 34.8 months for Arm 2. Only two patients experienced a bone fracture (one in each arm) resulting in no difference in freedom from any bone fracture (P=0.95), nor in QOL. BMD percent changes from baseline to 36 months were statistically improved with the use of zoledronic acid compared to observation for the lumbar spine (6% vs -5%, P<0.0001), left total hip (1% vs -8%, P=0.0002), and left femoral neck (3% vs -8%, P=0.0007).
  
  
  CONCLUSIONS
  For patients with advanced, non-metastatic prostate cancer receiving LHRH agonist and RT, the use of zoledronic acid was associated with statistically improved BMD percent changes. The small number of accrued patients resulted in decreased statistical power to detect any differences in the incidence of bone fractures or QOL.
authors.affiliation: Department of Radiation Oncology, Boston University Medical Center, Boston, MA, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Kachnic
authors.forename: S L
authors.initials: SL
authors.lastname: Pugh
authors.forename: P
authors.initials: P
authors.lastname: Tai
authors.forename: M
authors.initials: M
authors.lastname: Smith
authors.forename: E
authors.initials: E
authors.lastname: Gore
authors.forename: A B
authors.initials: AB
authors.lastname: Shah
authors.forename: A-G
authors.initials: AG
authors.lastname: Martin
authors.forename: H E
authors.initials: HE
authors.lastname: Kim
authors.forename: A
authors.initials: A
authors.lastname: Nabid
authors.forename: C A F
authors.initials: CA
authors.lastname: Lawton
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000009:adverse effects / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D004164:Diphosphonates / Q000627:therapeutic use*; D050723:Fractures, Bone / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D010024:Osteoporosis / Q000209:etiology* / Q000517:prevention & control*; D011471:Prostatic Neoplasms / Q000150:complications* / Q000473:pathology / Q000628:therapy; D016896:Treatment Outcome; D000077211:Zoledronic Acid
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid